RVX-297

Research use only, not for human use.

RVX-297 is a novel orally active, BD2 selective, BET bromodomain inhibitor.

RVX-297 is a novel orally active, BD2 selective, BET bromodomain inhibitor with Alpha Screen IC50 of 0.08, 0.05 and 0.02 uM for BRD2 (BD2), BRD3 (BD2) and BRD4 (BD2), respectively; displays about 50-fold selectivity over BD1; suppresses inflammatory gene expression in multiple immune cell types in culture; reduces pro-inflammatory mediators assessed in splenic gene expression and serum proteins in LPS model of inflammation.

RVX-297 (1-30 μM; 24 hours) decreases proinflammatory gene expression in synovial fibroblasts.RVX-297 displaces BET proteins from the promoters of sensitive genes and disrupted recruitment of active RNA polymerase II, a property shared with pan-BET inhibitors that nonselectively bind BET BDs. RVX-297 reduces gene expression of inflammatory mediators in vitro. RVX-297 suppresses IL-6 gene induction in human U937 macrophages, mouse primary B cells isolated from the spleen, mouse BMDMs, and THP-1 monocytes in a dose-dependent manner. RVX-297 represses IL-1β expression in LPS-stimulated mouse BMDMs, with an IC50 of 0.4-3 μM. RVX-297 inhibits MCP-1 expression in unstimulated human PBMCs with an IC50 of 0.4 μM. RVX-297 inhibits antigen stimulation of T cells and the induction of IL-17 expression. RT-PCR Cell Line:Synovial fibroblasts Concentration:1-30 μM Incubation Time:24 hours Result:Down regulated IL-6 and VCAM-1 gene expression in synovial fibroblasts.

RVX-297 (25-75 mg/kg; p.o.; per day for 6 day) inhibits progression of pathology in the rat collagen-induced arthritis model.RVX-297 (75-150 mg/kg) inhibits progression of pathology in the mouse collagen-induced arthritis model.RVX-297 suppresses cytokine production in LPS-treated mice. Animal Model:Female Lewis rats are 6-8 weeks old, approximately 150 g (rat collagen-induced arthritis)Dosage:25, 50, and 75 mg/kg Administration:P.o.; per day for 6 days Result:Prevented swelling and inflammation of the ankle and knee joints.

RVX297

Chromatin/Epigenetic

Bromodomain

Bromodomain

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1044871-04-6

423.513

C24H29N3O4

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (118.06 mM)

COC1=C(C(NC(C2=CC(C)=C(OCCN3CCCC3)C(C)=C2)=N4)=O)C4=CC(OC)=C1

2-(3,5-dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one

(-20℃)

With Ice Pack

≥ 2 years